The long-term objective of this project is to identify nutritional factors that can reduce the inflammatory component of obesity. Therapies to minimize obesity-related comorbidities are needed, and targeting inflammation may help slow the progression of obesity towards cardiovascular disease and insulin resistance. Adipose tissue is a source of inflammatory cytokines, and obesity is now viewed as a chronic, low-grade inflammatory state. Inflammation itself is a contributor to the chronic diseases associated with obesity. C- reactive protein (CRP) is a key marker of inflammation, and as a downstream marker it provides functional integration of upstream cytokine activation associated with inflammation. We have previously shown that vitamin C, but not vitamin E, reduces CRP in active and passive smokers and in nonsmokers. The reduction is seen primarily in persons with CRP e1.0 mg/L, the CDC threshold for elevated cardiovascular disease risk. We also found that 75% of obese nonsmokers had CRP e1.0 mg/L. The important observation of reduction in elevated CRP by vitamin C now needs to be confirmed in a rigorous study with adequate sample size, to permit justifiable conclusions about the potential usefulness of this agent in reducing inflammation in the obese. We will conduct a placebo-controlled, randomized trial in 552 healthy obese individuals with moderate CRP elevations (CRP e1.0 mg/L). Participants will be randomized to either 1000 mg/day vitamin C or placebo for a period of 2 months. We will also characterize the pathways through which this effect takes place by measuring cytokines and oxidative stress. This project is important because if our previous finding is confirmed in this population, it could offer a low-cost alternative to use of statins to reduce inflammation in persons without other risk factors. PUBLIC HEALTH RELEVANCE: Obesity is a prevalent inflammatory condition and major risk factor for many of the chronic diseases of aging. Confirming an anti-inflammatory effect of vitamin C is important because therapies to minimize obesity-related comorbidities are needed. Targeting the inflammatory component of obesity may help slow its progression towards insulin resistance and cardiovascular disease.